The proposed research projects are designed to determine whether known age-associated changes in CNS function and related pathophysiological alterations are correlated with and/or mediated by age-related changes in brain bioenergetics and cerebral metabolism. Our approach includes a combination of physiological, biochemical, and pharmacological studies involving the development of bio-optical techniques, i.e. surface fluorometry and reflectance spectrophotometry, to monitor intramitochondrial functional and bioenergetic activities in the intact brain of young and old animals. This approach will permit the detection of differences in the reduction/oxidation (redox) states of components of the respiratory chain, e.g. NAD/NADH ratios and cytochromes, during "resting" or non-stimulated conditions as well as during stress mediated states of brain activation by electrophysiological stimulation and/or pharmacologically induced alterations. By producing stress conditions and evaluating altered mechanisms in the metabolic and bioenergetic capabilities of neuronal tissue, we can test the hypothesis that changes in metabolic function lead to a diminished capacity of aging tissue to sustain maximal physiological efficiency particularly under conditions of energy demand. Studies of homeostatic anomalies and pathophysiological changes in CNS function with aging will enable us to further the concept of aging on a cellular and organismic level and to consider possibilities for pharmacological management of age-related difficulties in brain physiological and mental function. BIBLIOGRAPHIC REFERENCES: LaManna, J.C., A.L. Sylvia, D. Martel and M. Rosenthal. Fluorometric monitoring of the effects of adrenergic agents on oxidative metabolism in intact cerebral cortex. Neuropharmacology 15: 17-24, 1976. Sylvia, A.L. and M. Rosenthal. Metabolite levels in anesthetized and cerveau isole rat preparations. Fed. Proc. 35: 242, 1976.